Glucocorticoid receptor gene variants and lower expression of NR3C1 are associated with cocaine use

Addiction Biology
Andrea B SchoteBoris B Quednow

Abstract

Animal and cross-sectional human studies suggest that chronic cocaine use is associated with altered responsivity of the hypothalamic-pituitary-adrenal axis to stress. Moreover, increased susceptibility to stress has been proposed as an important factor for development, maintenance and relapse of cocaine addiction. As the glucocorticoid receptor gene (NR3C1) mediates genomic effects of the stress hormone cortisol, we investigated NR3C1 expression and the association of NR3C1 genotypes with cocaine use, addiction and comorbid psychiatric symptoms in 126 chronic cocaine users and 98 stimulant-naïve healthy controls. A comprehensive psychiatric assessment was performed including severity of depressive symptoms and current psychological distress. Whole blood NR3C1 mRNA levels were determined and six NR3C1 polymorphisms (rs10482605, rs41423247, rs10052957, rs6189, rs56149945 and rs6198) were genotyped. Compared to controls, cocaine users showed significantly lower NR3C1 expression (P < 0.001), which was not affected by NR3C1 genotypes. In controls, rs41423247 [P < 0.01, false discovery rate (FDR)-corrected], haplotype 2 and haplotype 3 (both P < 0.05, FDR-corrected) were associated with altered NR3C1 gene expression. Haplotype 3 (in...Continue Reading

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Citations

Aug 31, 2019·Journal of Neuroendocrinology·Alexis L FranksDonald B DeFranco
Jan 21, 2021·International Journal of Molecular Sciences·Dario KringelJörn Lötsch
Jun 17, 2021·Journal of Affective Disorders·Xing-Xing ChenYing Sun
Jul 19, 2021·The Journal of Steroid Biochemistry and Molecular Biology·Roza MotavalliJalal Etemadi
Oct 23, 2021·The International Journal of Neuropsychopharmacology·Clarissa D VoegelBoris B Quednow

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